This invention was made with the support of NIH Grant No. GM40036. The U.S. Government has certain rights in this invention.
Synthetic methodology which allows for a rapid increase in molecular complexity is extremely valuable in organic chemistry, particularly when it accommodates considerable functionality. Presently, carbon-carbon bond formation catalyzed by transition metal complexes is used extensively in organic synthesis. For example, the cross-coupling of 3,4-epoxy-l-alkenes and stoichiometric amounts of organolithium, -boron, -copper, -mercury, -nickel, and -palladium compounds provides an important route to allylic alcohols (eq 1 ). ##STR1##
For example, see R. C. Larock, Comprehensive Organic Transformations; VCH Publishers, Inc., New York (1989) at pages 123-124, and J. A. Marshall et al., Chem. Rev., 89, 1503 (1989). R. C. Larock et al., in Tetrahedron Lett., 27, 2211 (1986) have reported one example of the analogous arylation of 4,5-epoxy-1-pentene employing stoichiometric amounts of an arylmercurial and either stoichiometric or catalytic amounts of palladium salts (eq 2). ##STR2##
More recently, R. C. Larock et al., in J. Org. Chem., 55, 6244 (1990) reported that palladium catalyzes the cross-coupling of aryl halides, but not vinylic halides, and olefinic epoxides in which the two functional groups are separated by anywhere from one to ten carbons (eq 3). ##STR3##
However, any attempt to extend this procedure to vinylic epoxides must circumvent the known propensity of such epoxides to react with palladium(O) to form .pi.-allylpalladium species which can undergo attack by various nucleophiles, including formate, or rearrange to dienols or unsaturated carbonyl compounds (eq 4). ##STR4##
If competitive, these pathways would circumvent the desired allylic alcohol formation. For examples of such side reactions, see B. M. Trost et al., J. Amer. Chem. Soc., 103, 5969 (1981); M. Oshima et al., J. Amer. Chem. Soc., 111, 6280 (1989); and M. Suzuki et al., J. Amer. Chem. Soc., 101, 1623 (1979). Therefore, a need exists for a method to prepare substituted allylic alcohols from vinylic epoxides and aryl or vinyl halides.